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Questions for Dr. Kennedy
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sleep deprivation
Posted by: Helene
Date: February 3, 2002 1:39 PM

I have narcolepsy which, I believe in my case, is genetic. There have been several exciting discoveries about this disease in the past few years. One is that after a severe progression of the disease, the patient is left with very little hypocretin or orexin (different names for same neuropeptide) which plays a big role in wakefulness and appetite regulation. A newer discovery is that we are severely deficient in histamine producing neurochemicals. Many people with narccolepsy, of which I am one, get little to no stage 3 or 4 sleep as our sleep is fragmented, and we don't sleep more than an hour or 2 at any one time. HGH is produced during the stage 3 and 4, and after several years of little restorative sleep, I have aged what seems like 20 to 30 years, and I am constantly sick. There are no sleep specialists or neurologists who will discuss this possibilty with me because it is not included in the clinical guidelines which call for treatment with amphetamines and tricyclics. I cannot take tricyclics, and the amphetamines have lost most of their efficacy, and I was not able to stand the side effects of Modafinal, the newest stay awake drug. Any suggestions on how to proceed? I am 49 and I am unable to keep up with my friends who are mostly in their 80' and 90's.

RE: sleep deprivation
Posted by: Ron Kennedy, M.D.
Date: February 3, 2002 10:43 PM

The obvious thing to do regarding HGH would be to supplement and roll back the clock at that level. Hypocretin is under development - that is to synthesize it so that it is available for people with narcolepsy.

Until we can find answers, all we can offer people with narcolepsy are drugs to control their symptoms. We can counteract some of the sleepiness experienced by narcoleptics using stimulants such as Ritalin and Cylert or amphetamines, which activate dopamine receptors to increase the overall level of arousal. Another drug, Provigil, whose mechanism of action is not clear, may act by stimulating hypocretin/orexin neurons and other neural populations in the hypothalamus that in turn activate brain arousal systems. The downside is that such drugs are effective only for short periods and can cause unpleasant side effects, such as agitation, dry mouth and anxiety.

To prevent the cataplectic attacks of narcolepsy, physicians can prescribe agents that increase the availability of norepinephrine in the brain. These include monoamine oxidase inhibitors--which block the enzyme that destroys norepinephrine after it is released by neurons--and drugs such as Prozac, whose breakdown products activate norepinephrine receptors. Gamma hydroxybutyrate (GHcool smiley, whose mode of action is unclear, can also be effective against cataplexy.



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